This invention relates to coatings for surgical implants. In particular, the present invention relates to hydrophilic copolymers that are hydrophobically bound to the surface of surgical implants.
Both rigid and foldable implantable ophthalmic lens materials are known. The most common rigid material used in ophthalmic implants is polymethyl methacrylate (xe2x80x9cPMMAxe2x80x9d). Foldable intraocular lens (xe2x80x9cIOLxe2x80x9d) materials can generally be divided into three categories: silicone materials, hydrogel materials, and non-hydrogel (xe2x80x9chydrophobicxe2x80x9d) acrylic materials. See, for example, Foldable Intraocular Lenses, Ed. Martin et al., Slack Incorporated, Thorofare, N.J. (1993). For purposes of the present application, hydrophobic acrylic materials are acrylic materials that absorb less than approximately 5% water at room temperature.
Silicone and non-hydrogel acrylic materials used in ophthalmic implants can damage endothelial cells and perhaps other cells or tissues as well during or after the implant""s insertion in the eye. These materials are generally hydrophobic and/or tacky and can pull cells off of eye tissues that contact the implant. Particularly in the case of phakic IOL""s implanted between the capsular bag and the iris, there is significant potential for physical contact between the implant and surrounding cells or tissue even after the implant reaches its target location.
The present invention relates to hydrophilic coating compositions for surgical implants, particularly ophthalmic implants comprising silicone or non-hydrogel acrylic materials. More specifically, the present invention relates to a coating material for an implant where the coating material comprises a copolymer of 2-phenylethyl (meth)acrylate and N-vinyl pyrrolidone (xe2x80x9cNVPxe2x80x9d). The coating material is capable of absorbing from about 40 to about 90% water. Despite its relatively high water content, the coating material of the present invention is sufficiently tough to withstand folding or handling with forceps without rupturing.
The present invention also relates to a method for applying a coating comprising a copolymer of 2-phenylethyl (meth)acrylate and NVP to an implant""s surface, wherein the copolymer lacks a cross-linking monomer. The method comprises dissolving the copolymer in a solvent to form a coating solution, contacting the coating solution with the implant""s surface, and drying the coated implant.
Unless indicated otherwise, all amounts are expressed as weight %.
The coating material of the present invention is a copolymer of 2-phenylethyl (meth)acrylate and NVP. The coating material is attached to the substrate by means of hydrophobic or xe2x80x9cphysicalxe2x80x9d (i.e., non-covalent) cross-linking. The coating material is also intemally cross-linked by non-covalent cross-linking. The coating material is capable of absorbing from about 40 to about 90% water, preferably from about 65 to about 75% water. The proportion of the copolymer""s monomers will depend on the desired water content, with individual concentrations generally ranging from about 25 to about 60% for 2-phenylethyl (meth)acrylate and about 40 to about 75% for NVP. Copolymers of 2-phenylethyl methacrylate (xe2x80x9c2-PEMAxe2x80x9d) and NVP are preferred. In the preferred case where the desired water content is about 65-75%, the copolymeric coating material comprises from about 35 to about 45% 2-PEMA and from about 40 to about 50% NVP.
The copolymeric coating material is prepared by combining the 2-phenylethyl (meth)acrylate and NVP ingredients with a polymerization initiator (generally about 2% or less) to form a coating composition and curing the coating composition. Any type of polymerization initiator may be used, including thermal initiators and photoinitiators. A preferred initiator is the benzoylphosphine oxide initiator, 2,4,6-trimethyl-benzoyldiphenylophosphine oxide (xe2x80x9cTPOxe2x80x9d), which is activated by blue-light. Suitable thermal initiators include the conventional peroxides t-butyl peroctoate and bis-azoisobutronitrile. Suitable UV initiators include benzoin methyl ether and Darocur 1173.
In addition to the 2-phenylethyl (meth)acrylate, NVP, and polymerization initiator, the coating copolymers optionally include one or more ingredients selected from the group consisting of UV absorbers that are copolymerizable with the 2-phenylethyl (meth)acrylate and NVP ingredients; blue-light blocking colorants that are copolymerizable with the 2-phenylethyl (meth)acrylate and NVP ingredients; reactive plasticizers to minimize haze or crazing; and chain transfer agents to minimize cross-linking within the coating copolymer.
Ultraviolet absorbing chromophores can be any compound which absorbs light having a wavelength shorter than about 400 nm, but does not absorb any substantial amount of visible light. Suitable copolymerizable ultraviolet absorbing compounds are the substituted 2-hydroxybenzophenones disclosed in U.S. Pat. No. 4,304,895 and the 2-hydroxy-5-acryloxyphenyl-2H-benzotriazoles disclosed in U.S. Pat. No. 4,528,311. The most preferred ultraviolet absorbing compound is 2-(3xe2x80x2-methallyl-2xe2x80x2-hydroxy-5xe2x80x2-methyl phenyl)benzotriazole. Suitable polymerizable blue-light blocking chromophores include those disclosed in U.S. Pat. No. 5,470,932. If a bluelight activated polymerization initiator is chosen and a blue-light blocking colorant is added, the polymerization initiator identity or concentration may have to be adjusted to minimize any interference.
Suitable reactive plasticizers or softening agents include polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates. Methacrylates are preferred, with PEG(400)monomethylether monomethacrylate most preferred. If needed or desired, the amount of the reactive plasticizer will range from about 5 to about 25%. Depending on the implant""s function and the thickness of the coating, some degree of haze or crazing may be tolerated such that a reactive plasticizer may not be required.
The chain transfer agent, if present, is typically added in an amount ranging from 0.01 to 0.4%. Many chain transfer agents are known in the art. Examples of suitable chain transfer agents include 1-dodecanethiol and 2-mercaptoethanol.
After the coating copolymer is cured, it is purified by extraction to remove water-soluble components and low-molecular weight hydrophobic components. This can be accomplished by a two-stage extraction where the first stage is an aqueous extraction and the second is a non-aqueous extraction. The resulting coating copolymer is extracted in water, typically for 12-20 hours to remove aqueous extractables, such as N-vinyl pyrrolidone or low-molecular weight polyvinyl pyrrolidone. After the coating copolymer is extracted in water, it is dissolved in an organic solvent, such as methylene chloride. The resulting solution containing the dissolved polymer is added to a bath of volatile aliphatic solvent(s), such as heptane or hexane, to precipitate the coating copolymer. The precipitated coating copolymer is collected by, for example, filtration using a scintered glass filter and then dried, preferably under vacuum at room temperature.
After the coating copolymer is purified, a coating solution is prepared by dissolving the coating copolymer in a solvent or mixture of solvents, such as a 50:50 (parts by weight) mixture of ethanol and 2-pentanone. The solvent or mixture of solvents is preferably chosen to give a clear, homogenous coating solution where the chosen solvent or solvent mixture does not evaporate so quickly that it leaves a hazy coating.
The concentration of the coating copolymer in the coating solution will depend on the desired coating thickness. Other factors that will influence the thickness of the coating include the viscosity of the coating solution, the temperature of the coating solution and the implant, and the evaporation rate of the chosen solvent(s). In general, the coatings of the present invention will be no more than 1 xcexcm thick, and preferably will be about 0.5 xcexcm thick. A minimum coating thickness of about 0.01 xcexcm is likely necessary to allow the coating to survive any manipulation of the implant (such as the folding of an IOL) and any abrasion caused during implantation or extended residence at the target site in a patient. A concentration of coating copolymer of about 4-5% in the coating solution will typically produce a coating about 0.5 xcexcm thick in a dip-coating process.
The coating solution is applied to the implant by conventional techniques, such as spin- or dip-coating processes. Dip-coating is preferred. The implant is preferably dipped quickly so as to minimize any swelling of the implant caused by the solvent in the coating solution.
After the coating is applied to the implant, the coating is dried. A two-stage drying process is preferred. First, the coated implant is allowed to dry in air until most or all of the solvent has evaporated (generally xe2x89xa615 minutes). Second, the coated implant is baked at elevated temperature, about 40-100xc2x0 C., to eliminate as much of the remaining solvent as possible. A preferred drying process involves room temperature air drying for 15 minutes, followed by baking at 70xc2x0 C. for about 30 minutes.
The coating can be easily removed by a variety of organic solvents or solvent mixtures, including the same solvent used as the base in the preparation of the coating solution. The coating cannot be removed by water, however.
Before the coated implant is manipulated, the coating is preferably hydrated for several seconds to minimize crazing or other damage to the coating.
The implants suitable for coating with the hydrophilic coatings of the present invention are preferably made of hydrophobic acrylic materials, but could also be constructed of silicone or silicone-acrylic copolymers. Preferred hydrophobic acrylic materials are those polymeric materials described in U.S. Pat. Nos. 5,290,892 and 5,693,095, the entire contents of which are hereby incorporated by reference. In the case where the implant is an IOL, the coatings of the present invention may be used in conjunction with substrate materials intended for use as a xe2x80x9chardxe2x80x9d IOL (that is inserted in an unfolded state) or a xe2x80x9cfoldablexe2x80x9d or xe2x80x9csoftxe2x80x9d IOL (that is inserted in a folded or compressed state). Suitable IOL materials to be coated include those disclosed in U.S. Pat. Nos. 5,693,095 or 5,331,073. The coating may be applied to the entire IOL or to only a portion of the IOL. As used herein, xe2x80x9cimplantsxe2x80x9d includes contact lenses.
In order to prepare the implant material to be coated so that it is capable of receiving the coating, it may be necessary or desirable to expose the surface to be coated to a reactive plasma gas prior to applying the coating composition of the present invention. Suitable reactive plasma gases include oxidizing gases, such as oxygen gas. A suitable plasma chamber is the P2CIM B-Series plasma chamber made by Advanced Plasma Systems, Inc. Using such a chamber, suitable plasma parameters include: power=400 W, plasma gas=oxygen; pressure of the plasma gas=225 mTorr; exposure time=4-6 minutes.
The following examples are intended to be illustrative but not limiting.